Principles and Practice of Clinical Research
- 3rd Edition - May 31, 2012
- Editors: John I. Gallin, Frederick P Ognibene
- Language: English
The third edition of this innovative work again provides a unique perspective on the clinical discovery process by providing input from experts within the NIH on the principles and… Read more
The third edition of this innovative work again provides a unique perspective on the clinical discovery process by providing input from experts within the NIH on the principles and practice of clinical research. Molecular medicine, genomics, and proteomics have opened vast opportunities for translation of basic science observations to the bedside through clinical research. As an introductory reference it gives clinical investigators in all fields an awareness of the tools required to ensure research protocols are well designed and comply with the rigorous regulatory requirements necessary to maximize the safety of research subjects. Complete with sections on the history of clinical research and ethics, copious figures and charts, and sample documents it serves as an excellent companion text for any course on clinical research and as a must-have reference for seasoned researchers.
- Incorporates new chapters on Managing Conflicts of Interest in Human Subjects Research, Clinical Research from the Patient's Perspective, The Clinical Researcher and the Media, Data Management in Clinical Research, Evaluation of a Protocol Budget, Clinical Research from the Industry Perspective, and Genetics in Clinical Research
- Addresses the vast opportunities for translation of basic science observations to the bedside through clinical research
- Delves into data management and addresses how to collect data and use it for discovery
- Contains valuable, up-to-date information on how to obtain funding from the federal government
All individuals engaged in clinical research both student and researcher as well as physicians, dental investigators, PhD basic scientists, and members of allied health professions
Contributors
Preface
Acknowledgments
Chapter 1. A Historical Perspective on Clinical Research
The Earliest Clinical Research
Greek and Roman Influence
Middle Ages and Renaissance
Seventeenth Century
Eighteenth Century
Nineteenth Century
Twentieth Century and Beyond
Acknowledgment
Summary Questions
REFERENCES
Part I Ethical, Regulatory and Legal Issues
Chapter 2. Ethical Principles in Clinical Research
Distinguishing Clinical Research from Clinical Practice
What does Ethics have to do with Clinical Research?
History of Ethical Attention to Clinical Research
Codes of Research Ethics and Regulations
Ethical Framework for Clinical Research
Ethical Considerations in Randomized Clinical Trials
Conclusion
Summary Questions
REFERENCES
Chapter 3. Researching a Bioethical Question
Types of Bioethical Issues
Types of Bioethical Research Methodologies
Examples of Important Bioethical Research
Special Considerations in Bioethical Research
REFERENCES AND NOTES
Chapter 4. Integrity in Research
Guidelines for the Conduct of Research
Scientific Integrity and Misconduct
Mentor–Trainee Relationships
Data Acquisition, Management, Sharing, and Ownership
Research Involving Human and Animal Subjects
Collaborative Science
Conflict of Interest and Commitment
Peer Review
Publication Practices and Responsible Authorship
Acknowledgment
Summary Questions
REFERENCES
Chapter 5. Institutional Review Boards
Historical, Ethical, and Regulatory Foundations of Current Requirements for Research Involving Human Subjects
Institutional Review Boards
Clinical Researchers and IRBS
The Current IRB System Under Evaluation
Conclusion
Summary Questions
REFERENCES AND NOTES
Chapter 6. The Role of Independent Institutional Review Boards
History
Reasons to use an Independent IRB
Limitations of Independent IRBs
Selecting an Independent IRB
Working with an Independent IRB
Future Directions
Author’s Note
Resources
Summary Questions
REFERENCES
Chapter 7. The Regulation of Drugs and Biological Products by the Food and Drug Administration
Introduction
Background
Mission, Organization, and Terminology
Drug and Biologic Life Cycle
Summary Questions
Chapter 8. Data Management in Clinical Trials
The Research Team
Data Management Considerations during Protocol Design and Development
Data Collection
Auditing
Adverse Event Monitoring and Reporting
Legal And Regulatory Issues Related to Data Reporting
Follow-Up and Analysis
Record Retention
Conclusion
Summary Questions
REFERENCES
Chapter 9. Data and Safety Monitoring
Introduction
Description of the Data and Safety Monitoring Board
Data and Safety Monitoring Board Functions
Data and Safety Monitoring Board Decision Making
Examples
Conclusions
Summary Questions
REFERENCES
Chapter 10. Unanticipated Risk in Clinical Research
The Reasons
The Drug
The Target
The Trials
Cassandra Revealed
Extended Studies
Fiau Toxicity
Reassessing the Preclinical Studies
Research Oversight
The Investigations Begin
Scientific Misconduct
The FDA
The National Institutes of Health
The Institute of Medicine
The Media
The Congress
The Law
Epilogue
Acknowledgments
REFERENCES
Chapter 11. Legal Issues
Legal Issues Related to Informed Consent for Clinical and Research Care
Advance Directives/Substitute Consent
Children in Research
Medical/Research Records
Confidentiality
Legal Liability
Conflict of Interest
Authorship/Rights in Data
Summary Questions
Appendix
Instructions
Medical Record
NOTES AND REFERENCES
Further Reading
Chapter 12. Rules to Prevent Conflict of Interest for Clinical Investigators Conducting Human Subjects Research
Preventing Conflict of Interest in Clinical Research in the NIH Intramural Research Program
Preventing Conflict of Interest by Members of Institutional Review Boards
Appendix
Appendix 1
Summary Questions
REFERENCES
Chapter 13. National Institutes of Health Policy on the Inclusion of Women and Minorities as Subjects in Clinical Research
NIH Policy
Scientific Considerations and Implementation
Role of Peer Review
Role of the Institutional Review Board
Role of Volunteers and their Communities
Demographic Data on Subject Enrollment
Women of Childbearing Potential, Pregnant Women, and Children
What have We Learned
Conclusion
Summary Questions
REFERENCES AND NOTES
Chapter 14. Accreditation of Human Research Protection Programs
Brief History
Principles of Accreditation
What AAHRPP Expects from Organizations
What Organizations can Expect from AAHRPP
The Concept of a Human Research Protection Program
The Accreditation Standards
Summary Questions
REFERENCES
Chapter 15. The Role and Importance of Clinical Trial Registries and Results Databases
Introduction
Background
Current Policies
Registering Clinical Trials at ClinicalTrials.gov
Reporting Results to ClinicalTrials.gov
Using ClinicalTrials.gov Data
Conclusion
Summary/Discussion Questions
REFERENCES
Chapter 16. The Clinical Researcher and the Media
What Makes News In Science and Medicine?
Published Science—the Media’s Bread and Butter
Novelty
The Unexpected
Celebrity
Tragedy and Controversy
Impact
Why Talk to Reporters?
Why Reporters Want to Talk to You
Why you Should Talk to Reporters
Engaging the Media—The Process
A Word About E-Mail, the Internet, and New Media
If you Get a Call…
The Interview
What if you are Misquoted?
What the Public Does not Know About Science
Unexpected Questions
When the News is not Good
A Word About Investigative Reporters
The Freedom of Information Act (FOIA)
Embargoes
The Inglefinger Rule
Clinical Alerts
When to Contact your Institute’s/Center’s Communications Office
Conclusion
Summary Questions
Chapter 17. Clinical Research
The Patient–Scientist Partnership
Walking Away: Why Patients Refuse to Participate in Clinical Trials
The Trial Begins: Understanding the Patient Experience
Understanding the Caregiver
The Role of Palliative Care
Managing Difficult News
Effective Patient Communications: Recommendations and Considerations
The Assertive Patient: Ally in Scientific Research
Conclusion
FURTHER READING
Part II Biostatistics and Epidemiology
Chapter 18. Design of Observational Studies
Introduction
Ecological (Correlational) Studies
Case Reports and Case Series
Single Time Point Studies: Cross-Sectional Studies, Prevalence Surveys, and Incidence Studies
Case–Control Studies
Cohort Studies: Retrospective, Prospective, and Studies Nested Within a Cohort
Odds Ratios, Risk Ratios, Relative Risks, and Attributable Risk
Mistakes, Misconceptions, and Misinterpretations
Conclusions
Acknowledgments
Summary Questions
REFERENCES
Chapter 19. Design of Clinical Studies and Trials
The Purpose of Clinical Trials and Studies
Understanding the Spectrum of the Research Continuum
Clinical Trial Designs
Critical Issues in Clinical Study Design
Control Groups
Placebo Responses
Mistakes and Misconceptions
Conclusions
Acknowledgments
Summary Questions
REFERENCES
Chapter 20. Issues in Randomization
Introduction
History of the Randomized Trial
Randomization Methods
Issues in Implementation
Special Considerations
Conclusion
Acknowledgment
Summary Questions
REFERENCES
Chapter 21. Hypothesis Testing
Introduction
The Formulation of Statistical Hypotheses in the Motivating Examples
One-Sample Hypothesis Tests With Applications to Clinical Research
Two-Sample Hypothesis Tests With Applications to Clinical Research
Hypothesis Tests for the Motivating Examples
Common Mistakes in Hypothesis Testing
Misstatements and Misconceptions
Special Considerations
Conclusion
Acknowledgments
Summary Questions
REFERENCES
Chapter 22. Power and Sample Size Calculations
Introduction
Sample Size Calculations for Precision in Confidence Interval Construction
Sample Size Calculations for Hypothesis Tests: One Sample of Data
Sample Size Calculations for Hypothesis Tests: Paired Data
Sample Size Calculations for Hypothesis Tests: Two Independent Samples
Advanced Methods and Other Topics
Conclusion
Exercises
Acknowledgments
REFERENCES
Chapter 23. An Introduction to Survival Analysis
Introduction
Features of Survival Data
Survival Function
Common Mistakes
Conclusion
Summary Questions
REFERENCES
Chapter 24. Intermediate Topics in Biostatistics
1 Special Topics in Trial Design
2 Special Considerations in Data Analysis
3 Regression to the Mean
4 Diagnostic Testing
5 Special Considerations in Survival Analysis
6 Missing Data
7 Causal Inference in Observational Studies
8 Concluding Remarks
Summary Questions
Acknowledgement
REFERENCES
Chapter 25. Measures of Function and Health-related Quality of Life
Introduction to Function and Health-Related Quality of Life (HRQL) Measures
How are Function, QOL, and HRQL Measures Used?
Examples of Functional Measures and Health-Related Quality of Life Measures
Other Instruments to Consider
Importance of Quality of Life Measures for Health Care
Summary Questions
REFERENCES
Chapter 26. Large Clinical Trials and Registries—Clinical Research Institutes
Introduction
History
Phases of Evaluation of Therapies
Critical General Concepts
Expressing Clinical Trial Results
Concepts Underlying Trial Design
General Design Considerations
Legal and Ethical Issues
Hypothesis Formulation
Publication Bias
Statistical Considerations
Meta-Analysis and Systematic Overviews
Understanding Covariates and Subgroups
Therapeutic Truisms
Study Organization
Integration Into Practice
Controversies and Personal Perspective
The Future
Summary Questions
REFERENCES
Chapter 27. Meta-analysis of Clinical Trials
Techniques of Meta-Analysis
Meta-Analysis of Clinical Trials of Anti-Inflammatory Agents in Sepsis
Conclusions
Summary Questions
REFERENCES
Chapter 28. Using Large Datasets for Population-based Health Research
Introduction
Where Does the Data Come from?
Uses of Secondary Data in Health Research
Strengths
Limitations (and Solutions)
Surveys
Linking Data Sets
Ethical Considerations
Future Directions and Conclusions
Summary Questions
REFERENCES
Chapter 29. Development and Conduct of Studies
How to Choose a Study Design
Development and Importance of a Study Protocol
Equipoise
Manual of Operating Procedures
Reporting the Results
Conclusions
Acknowledgments
Summary Questions
REFERENCES
Part III Technology Transfer, Protocol Development, and Funding
Chapter 30. Overview of Technology Development
Introduction
Scenario: Disasters Waiting to Happen
The First and Biggest Mistake: Signing the Agreements
Agreements Not to Disclose: Trade Secrets and the Confidential Disclosure Agreement
Agreements to Transfer Materials
Collaboration and Inventions: The Cooperative Research and Development Agreement
Proprietary Materials: The Materials CRADA
Conclusion
Summary Questions
REFERENCES AND NOTES
Chapter 31. Patents and Patent Licenses
Introduction
Part One: Patents Generally
Core Concepts of us Patent Law
Basic Elements of the Patent Application Process
Part Two: Patents And Technology Transfer
Patenting and Licensing by Federal Agencies
Conclusion
Brief Glossary of Critical Terms in Patenting
Summary Questions
REFERENCES AND NOTES
Chapter 32. Writing a Protocol
Types of Protocols
Writing a Protocol
What Happens to your Protocol?
Essential Elements to Include in the Protocol
Summary
Summary Questions
REFERENCES
Chapter 33. Evaluating a Protocol Budget
Introduction
Requirements
Establishing a Protocol Budget
Summary
Chapter 34. Clinical Research Data
Introduction
Data as Surrogates
Types of Data
Data Standards
Data Capture, Storage, and Retrieval
Responsible Stewardship of Data
Cooperative Sharing Efforts
Summary
Summary Questions
REFERENCES
Chapter 35. Management of Patient Samples and Specimens
Successful Research Rests On A Foundation of Careful Planning
The Role of Pre-Analytic Variables in Research Using Patient Specimens
The Importance of Good Record Keeping
Specimen Tracking
Specimen Collection
Specimen Handling
Specimen Transit
Specimen Storage
Access To Patient Samples
Specimen Culling, Transfer of Collections, and Repository Closings
Summary Questions
REFERENCES
Chapter 36. Getting the Funding You Need to Support Your Research
Overview of NIH
The NIH Peer Review Process for Grants
Hints for Preparing Better Grant Applications
NIH Grant Programs for Clinical Researchers at Various Stages in their Careers
How to Stay Informed about NIH Peer Review
Chapter 37. Clinical Research from the Industry Perspective
History of the Pharmaceutical Industry
Components of the Pharmaceutical Industry
Issues Impacting Industry Clinical Research
Industry Outlook
Public–Private Opportunities
Summary Questions
REFERENCES
Chapter 38. Philanthropic Sector Support for Medical Research and Training
Introduction
Prior to 1950
1950 to Present
Alliances of Funders and Other Resources
Future Directions
Summary Questions
REFERENCES
Part IV Clinical Research Infrastructure
Chapter 39. Managing Clinical Risk and Measuring Participants’ Perceptions of the Clinical Research Process
Identifying and Managing Clinical Risk in the Clinical Research Environment
Assessing Clinical Research Participants’ Perceptions of the Clinical Research Experience
Conclusion
REFERENCES
Chapter 40. Integration of Specialized Research Services into Clinical Laboratory Operations
Introduction
Specialized Laboratory Services Developed for Clinical Research
Testing Approaches Used in Support of Clinical Research
Test Reporting
Examples of Specialized Laboratory Services Developed for Clinical Research
Summary
REFERENCES
Chapter 41. Imaging in Clinical Trials
Introduction: The Use of Imaging in Clinical Trials
Imaging Modalities
Imaging Interpretation
Imaging Core Laboratories
Incidental Imaging Findings
Risk Considerations From Imaging
Issues Regarding Sample Size
Picture Archiving and Communication System (PACS)
Role of the Imaging Specialist On the Clinical Trial Team
Summary
Summary Questions
REFERENCES
Chapter 42. Role of Blood Bank and Transfusion Medicine in Clinical Research
Introduction
Structure of the “Blood Bank”
The NIH Clinical Center’s Department of Transfusion Medicine
Summary Questions
REFERENCES
Chapter 43. Clinical Pharmacology and its Role in Pharmaceutical Development
Clinical Pharmacology as a Translational Discipline—Definition and Scope
Overview of Drug Development
Current State of Affairs in Drug Development
Contribution of Clinical Pharmacology
The Role of the Food and Drug Administration
Summary Questions
REFERENCES
Chapter 44. Career Paths in Clinical Research
Background
Student and Resident Training in Clinical Research
Clinical Research Curriculum
NIH Clinical Center Core Curriculum
Additional Educational Approaches and Support for Training
Conclusions
REFERENCES
Chapter 45. Clinical Research Nursing
Introduction
Clinical Research Nursing: A New Practice Specialty
Defining and Documenting the Specialty of Clinical Research Nursing
Legal Scope of Practice Issues
Tools to Assist a Principal Investigator in Staffing a Study
Future Considerations
Summary/Discussion Questions
REFERENCES
Chapter 46. Clinical Research Applications of Health Disparities Science in Community Settings
Background
Clinical Research Studies that can be Conducted in Community Settings
Health Services Research
Patient-Oriented Research
Steps to Consider When Conducting Clinical Research in Community Settings
Community Engagement, Collaboration, and Participatory Research
Future Directions
Summary Questions
REFERENCES AND NOTES
Chapter 47. Issues and Challenges for Clinical Research in International Settings
Introduction
Historical Perspectives
Challenges
Proffered Solutions
Conclusion
Summary Questions
REFERENCES
Chapter 48. The Power of an Undiagnosed Diseases Program in a Clinical Research Enterprise
Introduction
Mechanics
Cases
Genetics
Publicity
Future
Insights
Acknowledgments
Summary Questions
REFERENCES
Chapter 49. Human Genome Project, Genomics, and Clinical Research
Overview
Genetic Models
Complex Trait Dissection
Sample Collection and Informed Consent
Approach to Genotyping
Linkage Analysis
Association and Linkage Disequilibrium
Gene Identification
Integration of Genetics into Medical Practice
Summary
Acknowledgments
Summary Questions
REFERENCES
Chapter 50. Harnessing Information Using Genomic Platforms
Introduction
SNP Arrays
Whole Exome Sequencing
Methylation
Summary/Discussion Questions
REFERENCES
APPENDIX 1. Answer Key to Summary Questions
Chapter 1
Chapter 2
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Chapter 8
Chapter 9
Chapter 11
Chapter 12
Chapter 13
Chapter 14
Chapter 15
Chapter 16
Chapter 18
Chapter 19
Chapter 20
Chapter 21
Chapter 23
Chapter 24
Chapter 25
Chapter 26
Chapter 27
Chapter 28
Chapter 29
Chapter 30
Chapter 31
Chapter 32
Chapter 34
Chapter 35
Chapter 37
Chapter 38
Chapter 41
Chapter 42
Chapter 43
Chapter 44
Chapter 45
Chapter 46
Chapter 47
Chapter 48
Chapter 49
Chapter 50
APPENDIX 2. Principles and Practice of Clinical Research, 3rd Edition Acronyms by Chapter
Chapter 1 (Dr. J.I. Gallin)
Chapter 2 (Dr. Grady)
Chapter 3 (Dr. Emanuel)
Chapter 4 (Dr. Colbert)
Chapter 5 (Dr. Wichman)
Chapter 6 (Dr. Rosenfeld)
Chapter 7 (Dr. Zoon)
Chapter 8 (Ms. St. Germain)
Chapter 9 (Dr. Friedman)
Chapter 10 (Dr. Straus)
Chapter 11 (Patricia Kvochak, Esq.)
Chapter 12 (Dr. Nussenblatt)
Chapter 13 (Dr. Kelty)
Chapter 14 (Dr. Speers)
Chapter 15 (Dr. Zarin)
Chapter 16 (Mr. Burklow)
Chapter 17 (Ms. Butler)
Chapter 18 (Dr. Johnson)
Chapter 19 (Dr. Stoney)
Chapter 20 (Dr. Shaw)
Chapter 21 (Dr. Johnson)
Chapter 22 (Dr. Borkowf)
Chapter 23 (Dr. Johnson)
Chapter 24 (Dr. Johnson)
Chapter 25 (Dr. Gerber)
Chapter 26 (Dr. Califf)
Chapter 27 (Dr. Sun)
Chapter 28 (Dr. Chan)
Chapter 29 (Dr. Stoney)
Chapter 30 (Mr. Goldstein)
Chapter 31 (Mr. Goldstein)
Chapter 32 (Dr. Nussenblatt)
Chapter 33 (Ms. Matula)
Chapter 34 (Dr. Cimino)
Chapter 35 (Dr. Pitt)
Chapter 36 (Dr. Bartlett)
Chapter 37 (Ms. Resnik)
Chapter 38 (Dr. E.K. Gallin)
Chapter 39 (Ms. Lee)
Chapter 40 (Dr. Remaley)
Chapter 41 (Dr. Bluemke)
Chapter 42 (Dr. Klein)
Chapter 43 (Dr. Lertora)
Chapter 44 (Dr. Ognibene)
Chapter 45 (Dr. Hastings)
Chapter 46 (Dr. Dankwa-Mullan)
Chapter 47 (Dr. Olopade)
Chapter 48 (Dr. Gahl)
Chapter 49 (Dr. Korf)
Chapter 50 (Dr. Hart)
Index
- Edition: 3
- Published: May 31, 2012
- Language: English
JG
John I. Gallin
Dr. John Gallin was appointed to the dual roles of National Institutes of Health (NIH) Associate Director for Clinical Research and inaugural Chief Scientific Officer, the Clinical Center in August 2016. He served as the Director NIH Clinical Center from 1994-2017 after serving 9 years as Scientific Director of the National Institute of Allergy and Infectious Diseases (NIAID) and 12 years as Chief of the Laboratory of Host Defenses. During his tenure as Director of the NIH Clinical Center, Dr. Gallin helped to lead the design, construction, and activation of the Mark O. Hatfield Clinical Research Center, the largest hospital in the world totally dedicated to clinical research. He also oversaw the establishment of a new curriculum for clinical research training, now offered globally reaching over 25,000 students annually in 168 countries, and the development of new information systems for biomedical, translational and clinical research. In 2011, Dr. Gallin accepted, on behalf of the NIH Clinical Center, the Lasker–Bloomberg Public Service Award for its rich history of medical discovery through clinical research. His primary research interests are rare immune disorders of phagocytes, with a focus on chronic granulomatous disease (CGD). His laboratory described the genetic basis for several forms of CGD and other disorders of phagocytes and has done pioneering research that has reduced life-threatening bacterial and fungal infections in patients with these disorders. He has published more than 380 articles in scientific journals and edited two textbooks – Inflammation, Basic Principles and Clinical Correlates (Lippincott, Williams, and Wilkins, 1999, 3rd edition) and Principles and Practice of Clinical Research (Academic Press, 4th edition 2018). He has received numerous awards and honors for his accomplishments and in 2022 received the Weill Cornell Medical College Alumni Award of Distinction, the medical college’s most prestigious alumni award. Dr. Gallin is a member of the American Society for Clinical Investigation, the Association of American Physicians, the National Academy of Medicine of the National Academy of Sciences, a Master of the American College of Physicians, and a Fellow of the Royal College of Physicians-London. He retired from his administrative positions in 2023 and is now an Adjunct Senior Investigator at NIH in the Laboratory of Clinical Immunology and Microbiology in the National Institute of Allergy and Infectious Diseases.
Affiliations and expertise
Chief Scientific Officer, Clinical Center, Associate Director for Clinical Research, National Institutes of Health, Bethesda, MD, USAFO
Frederick P Ognibene
Affiliations and expertise
MD, MCCM, FACP, Deputy Director, Educational Affairs and Strategic Partnerships, NIH Clinical Center and Director, Office of Clinical Research Training and Medical Education, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USARead Principles and Practice of Clinical Research on ScienceDirect